4D Printing of Multi‐Responsive Membrane for Accelerated In Vivo Bone Healing Via Remote Regulation of Stem Cell Fate

Adhesions are important cell structures required to transduce a variety of chemical and mechanics signals from outside-in and vice versa, all of which regulate cell behaviors, including stem cell differentiation (1). Though most biomaterials are coated with an adhesive ligand to promote adhesion, they do not often have a uniform distribution that does not match the heterogeneously adhesive extracellular matrix (ECM) in vivo (2). We have previously shown that diblock copolymer (DBC) mixtures undergo interface-confined de-mixing to form nanodomins of one copolymer in another (3). Here we demonstrate how diblock copolymer mixtures can be made into foams with nanodomains to better recapitulate native ECM adhesion regions and influence cell adhesion.

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Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Science ◽

10.1126/science.aax1694 ◽

2019 ◽

Vol 366 (6466) ◽

pp. 734-738 ◽

Cited By ~ 11

Author(s):

Antoine de Morree ◽

Julian D. D. Klein ◽

Qiang Gan ◽

Jean Farup ◽

Andoni Urtasun ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Messenger Rna ◽

Adult Stem Cells ◽

Alternative Polyadenylation ◽

Quiescent State ◽

Stem Cell Fate ◽

Activation Rate

Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

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Constructing stem cell microenvironments using bioengineering approaches

Physiological Genomics ◽

10.1152/physiolgenomics.00099.2013 ◽

2013 ◽

Vol 45 (23) ◽

pp. 1123-1135 ◽

Cited By ~ 29

Author(s):

David A. Brafman

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Disease Modeling ◽

Mechanical Stimuli ◽

Culture Methods ◽

Stem Cell Fate ◽

And Function

Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

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Molecular imaging for In vivo tracking of stem cell fate

Macromolecular Research ◽

10.1007/s13233-014-2184-9 ◽

2014 ◽

Vol 22 (11) ◽

pp. 1141-1151 ◽

Cited By ~ 1

Author(s):

Kyoung Soo Lee ◽

Eun Ji Kim ◽

Ji Suk Choi ◽

Ick Chan Kwon ◽

Yong Woo Cho

Keyword(s):

Stem Cell ◽

Molecular Imaging ◽

Cell Fate ◽

Stem Cell Fate

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Synthetic Extracellular Microenvironment for Modulating Stem Cell Behaviors

Biomarker Insights ◽

10.4137/bmi.s20057 ◽

2015 ◽

Vol 10s1 ◽

pp. BMI.S20057 ◽

Cited By ~ 4

Author(s):

Prafulla Chandra ◽

Sang Jin Lee

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Bioactive Molecules ◽

Stem Cell Fate ◽

Cell Behaviors ◽

Extracellular Microenvironment ◽

Promising Source

The innate ability of stem cells to self-renew and differentiate into multiple cell types makes them a promising source for tissue engineering and regenerative medicine applications. Their capacity for self-renewal and differentiation is largely influenced by the combination of physical, chemical, and biological signals found in the stem cell niche, both temporally and spatially. Embryonic and adult stem cells are potentially useful for cell-based approaches; however, regulating stem cell behavior remains a major challenge in their clinical use. Most of the current approaches for controlling stem cell fate do not fully address all of the complex signaling pathways that drive stem cell behaviors in their natural microenvironments. To overcome this limitation, a new generation of biomaterials is being developed for use as three-dimensional synthetic microenvironments that can mimic the regulatory characteristics of natural extracellular matrix (ECM) proteins and ECM-bound growth factors. These synthetic microenvironments are currently being investigated as a substrate with surface immobilization and controlled release of bioactive molecules to direct the stem cell fate in vitro, as a tissue template to guide and improve the neo-tissue formation both in vitro and in vivo, and as a delivery vehicle for cell therapy in vivo. The continued advancement of such an intelligent biomaterial system as the synthetic extracellular microenvironment holds the promise of improved therapies for numerous debilitating medical conditions for which no satisfactory cure exists today.

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A Wnt Signal Regulates Stem Cell Fate and Differentiation in vivo

Neurodegenerative Diseases ◽

10.1159/000101891 ◽

2007 ◽

Vol 4 (4) ◽

pp. 333-338 ◽

Cited By ~ 33

Author(s):

Nilima Prakash ◽

Wolfgang Wurst

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Stem Cell Fate ◽

Wnt Signal

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Arginine Methylation by PRMT1 Regulates Muscle Stem Cell Fate

Molecular and Cellular Biology ◽

10.1128/mcb.00457-16 ◽

2016 ◽

Vol 37 (3) ◽

Cited By ~ 24

Author(s):

Roméo Sébastien Blanc ◽

Gillian Vogel ◽

Xing Li ◽

Zhenbao Yu ◽

Shawn Li ◽

...

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Muscle Regeneration ◽

Myogenic Differentiation ◽

Arginine Methylation ◽

Muscle Stem Cell ◽

Stem Cell Fate ◽

Protein Arginine Methyltransferase 1

ABSTRACT Quiescent muscle stem cells (MSCs) become activated in response to skeletal muscle injury to initiate regeneration. Activated MSCs proliferate and differentiate to repair damaged fibers or self-renew to maintain the pool and ensure future regeneration. The balance between self-renewal, proliferation, and differentiation is a tightly regulated process controlled by a genetic cascade involving determinant transcription factors such as Pax7, Myf5, MyoD, and MyoG. Recently, there have been several reports about the role of arginine methylation as a requirement for epigenetically mediated control of muscle regeneration. Here we report that the protein arginine methyltransferase 1 (PRMT1) is expressed in MSCs and that conditional ablation of PRMT1 in MSCs using Pax7CreERT2 causes impairment of muscle regeneration. Importantly, PRMT1-deficient MSCs have enhanced cell proliferation after injury but are unable to terminate the myogenic differentiation program, leading to regeneration failure. We identify the coactivator of Six1, Eya1, as a substrate of PRMT1. We show that PRMT1 methylates Eya1 in vitro and that loss of PRMT1 function in vivo prevents Eya1 methylation. Moreover, we observe that PRMT1-deficient MSCs have reduced expression of Eya1/Six1 target MyoD due to disruption of Eya1 recruitment at the MyoD promoter and subsequent Eya1-mediated coactivation. These findings suggest that arginine methylation by PRMT1 regulates muscle stem cell fate through the Eya1/Six1/MyoD axis.

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